Proteome analysis of leaf, stem and callus in Viscum album and identification of lectins and viscotoxins with bioactive properties

Abstract

Mistletoes are semiparasite plants containing pharmaceutical proteins with applications in cancer treatment. Previous research has demonstrated that somaclonal variation can lead to the biosynthesis of novel proteins from mistletoe callus cultures. The protein content of Viscum album subsp. abietis tissues and biotechnologically propagated calluses, was analyzed to identify proteins with putative anticancer properties. In addition, evolutionary relations among linked species to Viscum were studied. Calluses were propagated from stem explants. The protein extracts mass spectra were processed with Proteome Discoverer and a search was performed using as reference the Uniprot V. album reviewed database. A phylogenetic tree was reconstructed using the LG amino acid substitution model by homologous sequences for Beta galactoside-specific lectin 2. The homology modeling of the Beta-galactoside-specific lectin 2 was carried out using Modeller software. Considerable differences were observed by comparing the protein content of the calluses and the maternal tissues. Four mistletoe lectins, six viscotoxins and the chitin binding lectin-cbML were identified within the species tissues. An in silico phylogenetic and structural study provides insights to the role of these lectins and the mechanism of semiparasite survival and evolution, towards a novel anticancer and immune system modulation pipeline. Callogenesis exhibited protein biosynthesis alterations and novel protein isoforms expression. Phyllogenetic analysis revealed evolutionary relations primarily within the Viscum genus and other species containing 2-ribosome inactivating proteins. The homology modeling of the mistletoe lectin 2 revealed possible structure related anticancer properties. In conclusion, mistletoe calluses were shown to possess a unique protein biosynthetic profile compared to donor plant tissues.

Key message

Protein identification within V. album tissues and calluses highlighted evolutionary relations in species containing 2-RIP lectins and proteins with putative anti-malignant properties.

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Abbreviations

2-RIPs:

2 Ribosome-inactivating proteins

BA:

Benzyl adenine

CAN:

Acetonitrile

DTE:

Dithiothreitol

FASP:

Filter aided sample preparation

FDR:

False discovery rate

IPG:

Immobilized pH gradient

LC-HRMS/MS:

Liquid chromatography-tandem high resolution mass spectrometry

ML:

Mistletoe lectin

MS:

Mass spectra

NAA:

1-Naphthaleneacetic acid

RT:

Room temperature

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Conceptualization, VT, SM, JZ, DV and SK; methodology, VT, SM, MM, RS, JZ, AT and GM; software, DM; formal analysis, DM, AT; data curation, DM, AT; writing—original draft preparation, VT, SM, DV, JZ and GM; writing—review and editing, VT, SM, MM, RS, JZ, AT, GM, DV and SK; supervision, JZ, AT, DV, SK.

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Correspondence to Sophie Mavrikou or Spyridon Kintzios.

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Communicated by Silvia Moreno.

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Tsekouras, V., Mavrikou, S., Vlachakis, D. et al. Proteome analysis of leaf, stem and callus in Viscum album and identification of lectins and viscotoxins with bioactive properties. Plant Cell Tiss Organ Cult 141, 167–178 (2020). https://doi.org/10.1007/s11240-020-01777-7

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Keywords

  • Anticancer proteins
  • Callus
  • Mistletoe
  • Phyllogenetic tree
  • Proteome
  • Viscum album